The present invention relates to a method for processing of hydrogen for the reductive acylation of nitro, azido and cyano arenes. More particularly, this invention relates to an improved process for the preparation of amides and anilides using C3-C7 carboxylic acids as proton source/acylating agents employing Fe3+-montmorillonite as a catalyst.
This invention particularly relates to an eco-friendly process for reductive acylation of nitro, azido and cyano arenes using metal cation exchanged montmorillonite as a catalyst dispensing with the use of stiochiometric amounts of corrosive salts as reagents. The reductive acylated products are important intermediates in the preparation of drugs and pharmaceuticals.
Reference is made to Li et al., Journal of American Chemical Society; 726,124,2002 wherein enzymes are known to produce and consume hydrogen. The inherent disadvantages in this process are the electrons are supplied by H-clusters.
Reference is made to Cammack, Nature; 214, 397, and 1999 wherein [Fe]-hydrogenase enzyme is known to produce hydrogen, while the [Ni-Fe]-hydrogenase consumes hydrogen. The inherent disadvantages in this process are complex and tedious synthetic protocols. The hydrogenase models are developed to produce hydrogen substoichiometrically.
Reference is made to Nomura, Journal of Molecular Catalysis A., 1, 130, 1998 wherein reduction of nitroarenes is carried out using carbonyl complexes as catalysts under carbon monoxide pressures. The inherent disadvantage in this process is the use of non-regenerable expensive carbonyl complexes in stoichiometric quantities or expensive catalysts with hydrogen or CO pressure.
Reference is made to Wantanabe et al; Journal of Organic Chemistry 4451, 49, 1984 wherein reductive acylation of nitrobenzene is carried out by using platinum complexes under carbon monoxide pressure. The inherent disadvantages in this process are use of expensive platinum complexes and high CO pressure.
Reference is made to Kamal et al; Tetrahedron Letters, 7743, 41, 2000 wherein azides are reduced to amines by using stiochiometric quantities of FeSO4 in ammonia solution. The major drawback in this process is the reduction of azo compounds induced by non-regenerable stoichiometric hydride reagents.
The main object of the present invention is to provide a method for the processing of hydrogen for the reductive acylation of substituted nitro, azido and cyano arenes which obviates the drawbacks detailed above.
It is another object of the present invention to provide a novel and ecofriendly process for the production and consumption of hydrogen for the reductive acylation of substituted nitro, azido and cyano arenes.
It is a further object of the invention to provide a novel, economic and ecofriendly process for the reductive acylation of nitro, azido and cyano compounds.
It is yet another object of the invention to provide a process for the reductive acylation of substituted nitro, azido and cyano arenes which dispenses with the use of corrosive and stiochiometric quantities of non-regenerable expensive carbonyl complexes in stiochiometric quantities or expensive catalysts with hydrogen or CO pressure.
It is yet another object of the invention to provide a process for the reductive acylation of substituted nitro, azido and cyano arenes with good selectivity and yields.
It is yet another object of the invention to provide a process for the reductive acylation of substituted nitro, azido and cyano arenes wherein the catalyst can be recycled without significant loss of activity.
The novelty of the present invention provides resides in the production of hydrogen and consumption in the reductive acylation of nitro, azido, and cyano compounds using carboxylic acid as a proton source/acylating agents and iodide anion as electron source by metal exchanged montmorillonite catalyst under reflux conditions.
Promotive effect of montmorillonite, a prebiotic material and low redox potential of iron, and abundance of both these materials at cheaper cost prompted its use in the present studies. Higher yields and selectivities are obtained towards amides and anilides, when Fe3+-montmorillonite as synthesized is used in the reductive acylation of nitro, azido and cyano arenes in carboxylic acid solvent. Since anilides and amides are the desired starting materials for the synthesis of drugs, pharmaceuticals, this invention is timely and appropriate. Thus earlier papers, patents fell short of expectations for commercial reality and economics of the process. Thus, this invention offers the best techno-economic route for the synthesis of amides and anilides intermediates for drugs and pharmaceuticals.
Accordingly, the present invention provides a method for the processing of hydrogen used in the reductive acylation of nitro, azido, and cyano arenes comprising reacting C3-C7 carboxylic acid as an acylating agent/proton source and iodide as electron source using metal exchanged montmorillonite as a catalyst at a temperature in the range of 116-200xc2x0 C. for a time period in the range of 0.5-24 h, recovering the catalyst by filtration for reuse and recovering the acylated product.
In an embodiment of the invention, the processing of hydrogen comprises production of hydrogen at room temperature and consumption of hydrogen at higher temperatures.
In an embodiment of the invention, the temperature used for simultaneous production and consumption in the reductive acylation of substituted nitro, azido and cyano arenes is in the range of 25-200xc2x0 C.
In an embodiment of the invention, the metal ion used for exchange on montmorillonite is selected from the group consisting of Fe3+, Cu2+, Ce3+, Zr4+ and Al3+
In an embodiment of the invention, the production and consumption of hydrogen is catalysed by the same catalyst.
In an embodiment of the invention, the production of hydrogen is by the reduction of proton generated from the carboxylic acid.
In another embodiment of the invention, the reduction of proton generated from carboxylic acid is effected at room temperature by Mn+-montmorillonte where Mn+ is selected from Fe3+, Cu2+, Ce3+, Zr4+ and Al3+.
In another embodiment of the invention the nitro, azido or cyano arenes used for the reductive acylation reactions comprise substituted aromatic compounds selected from the group consisting of methyl, ethyl, propyl, halogen, acid, aryl and heteroaryl.
In yet another embodiment of the invention, the quantity of the catalyst is 5 to 20% by weight with respect to the substrate.
In another embodiment of the invention the C3-C7 carboxylic acid is selected from the group consisting of propionic acid to heptanoic acid.
In another embodiment of the invention, the iodide anion used as electron source is sodium iodide.
In another embodiment of the invention, the ratio of nitro, azido or cyano compounds to acylating agent is 1:4 to 1:8
In a further embodiment of the invention, the ratio of nitro and azido compounds to sodium iodide is 1:2 to 1:6
In yet another embodiment of the invention the ratio of cyano compounds to sodium iodide is 1:3 to 1:6
In another embodiment of the invention, the reaction of nitro and cyano compounds is effected at a temperature of 160-200xc2x0 C.
In another embodiment of the invention, the reaction of azido compounds is effected at a temperature of 116-160xc2x0 C.
In still another embodiment of the present invention, the reaction is effected for a period of 0.5-24 hrs.
The invention provides a method for the processing of hydrogen for the reductive acylation of substituted nitro, azido and cyano arenes, by reacting C3-C7 carboxylic acids as acylating agents/proton sources, iodide ion as electron source, employing metal cation exchanged montmorillonite as catalyst generally at a temperature in the range of 116-200xc2x0 C. for a period of 0.5-24 h, and recovering the catalyst by filtration for re-use and the acylated products by conventional methods. The processing of hydrogen comprises production of hydrogen at room temperature and consumption of hydrogen at higher temperatures. Generally, both the production and consumption of hydrogen is catalysed by the same catalyst. Hydrogen is produced by the reduction of proton generated from carboxylic acid.
The process of the invention dispenses with the use of corrosive and non-regenerable stoichiometric hydride reagents or under hydrogen pressure in the presence of expensive catalysts, and non-regenerable expensive carbonyl complexes in stoichiometric quantities or using expensive catalysts with hydrogen or CO pressure.
Another object of the present invention is to provide a process for the preparation of amides and anilides wherein the selectivity and conversions are good and the work up procedure is simple. The reduction of proton generated from carboxylic acid is effected at room temperature by Mn+-montmorillonte catalyst where Mn+ is preferably Fe3+, Cu2+, Ce3+, Zr4+, or Al3+. The montmorillonite or metal exchanged montmorillonite are used as catalysts for the reductive acylation of nitro, azido, and cyano arenes. The catalyst can be used for several cycles with consistent activity.
The C3-C7 carboxylic acids used as acylating agents/proton sources are preferably selected from propionic acid to heptanoic acid. Sodium iodide is a preferred electron source. In an embodiment of the present invention, the temperature used for simultaneous production and consumption of hydrogen in the reductive acylation of substituted nitro, azido and cyano arenes is in the range of 25-200xc2x0 C. The nitro, azido, cyano arenes used for the reductive acylation reactions are substituted aromatic compounds selected from methyl, ethyl, propyl, halogen, acid, aryl and heteroaryl.
The quantity of the catalyst is 5 to 20% by weight with respect to the substrate. The ratio of nitro, azido and cyano compounds to acylating agent is preferably 1:4 to 1:8. More particularly, the ratio of nitro and azido compounds to sodium iodide is preferably 1:2 to 1:6 and the ratio of cyano compounds to sodium iodide is 1:3 to 1:6. The reaction of nitro and cyano compounds is preferably effected at a temperature of 160-200xc2x0 C. and the reaction of the azido compounds is effected at a temperature of 116-160xc2x0 C.